Pletneva Maria, Fan Hongni, Park Jang-June, Radojcic Vedran, Jie Chunfa, Yu Yanxing, Chan Camie, Redwood Alec, Pardoll Drew, Housseau Franck
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.
Cancer Res. 2009 Aug 15;69(16):6607-14. doi: 10.1158/0008-5472.CAN-09-0508.
IFN-producing killer dendritic cells (IKDC) represent a recently discovered cell type in the immune system that possesses a number of functions contributing to innate and adaptive immunity, including production of type 1 and 2 IFNs, interleukin (IL)-12, natural killing, and ultimately antigen presentation to naïve T cells. Here, we compared in vitro and in vivo responses of mouse IKDC, conventional dendritic cells (DC), and natural killer (NK) cells to murine cytomegalovirus infection and found distinct functions among these cell subsets. Upon recognition of infected fibroblasts, IKDC, as well as NK, produced high level of IFN-gamma, but unlike NK, IKDC simultaneously produced IL-12p40 and up-regulated MHC class II (MHC-II) and costimulatory molecules. Using MHC-II molecule expression as a phenotypic marker to distinguish activated IKDC from activated NK, we further showed that highly purified MHC-II(+) IKDC but not NK cross-present MHC class I-restricted antigens derived from MCMV-infected targets to CD8(+) T cells in vitro and in vivo. Our findings emphasize the unique nature of IKDC as a killer antigen-presenting cell directly linking innate and adaptive immunity.
产生干扰素的杀伤性树突状细胞（IKDC）是免疫系统中最近发现的一种细胞类型，它具有许多有助于先天免疫和适应性免疫的功能，包括产生1型和2型干扰素、白细胞介素（IL）-12、自然杀伤作用，以及最终向初始T细胞呈递抗原。在此，我们比较了小鼠IKDC、传统树突状细胞（DC）和自然杀伤（NK）细胞在体外和体内对鼠巨细胞病毒感染的反应，发现这些细胞亚群具有不同的功能。在识别受感染的成纤维细胞后，IKDC以及NK细胞产生高水平的干扰素-γ，但与NK细胞不同的是，IKDC同时产生IL-12p40，并上调MHC II类（MHC-II）分子和共刺激分子。利用MHC-II分子表达作为一种表型标志物来区分活化的IKDC和活化的NK细胞，我们进一步表明，高度纯化的MHC-II(+) IKDC而非NK细胞，能够在体外和体内将源自MCMV感染靶标的MHC I类限制性抗原交叉呈递给CD8(+) T细胞。我们的研究结果强调了IKDC作为一种直接连接先天免疫和适应性免疫的杀伤性抗原呈递细胞的独特性质。
